脂毒性作用与胰岛β细胞功能损伤

胰岛素抵抗和胰岛β细胞分泌缺陷是2型糖尿病发病机制的两个主要环节。近年研究显示，长期高血脂可影响胰岛β细胞功能，称为脂毒性。脂毒性能进一步损害葡萄糖内环境稳定，最终导致2型糖尿病发生。生理条件下，游离脂肪酸(FFA)能刺激胰岛β细胞释放胰岛素。但实验证明，长期暴露于FFA中则损害胰岛β细胞释放胰岛素的功能，其可能机制有以下几方面。     

IGF—l、IGF—BP—l、IGF—BP—3与糖尿病及糖尿病微血管并发症

糖尿病影响循环中胰岛素样生长因子的水平和活性，不同类型的糖尿病对胰岛素样生长因子活性的影响是不同的。糖尿病患者体内胰岛素样生长因子的紊乱，可能参与糖尿病肾病、糖尿病视网膜病变的发生、发展。胰岛索样生长因子结合球蛋白-1可能对微血管病变起保护作用，胰岛素样生长因子结合球蛋白-3参与微血管病变的发病机制不明。     

胰岛素受体底物与2型糖尿病关系的研究进展

有效地改善胰岛素抵抗和阻止β细胞分泌功能的下降将可能延缓2型糖尿病的发生。胰岛素受体底物（IRS）家族蛋白是维持β细胞存活的重要蛋白质。近年来的研究发现,IRS与2型糖尿病胰岛素抵抗和β细胞分泌胰岛素功能有密切关系。并且越来越多的学者对IRS在2型糖尿病的发病中的作用机制以及信号传导通路进行了深入的研究。IRS在2型糖尿病发病中的重要作用决定了它可能成为糖尿病药物开发的靶点之一。我们就胰岛素受体底物与2型糖尿病关系的研究进展作一综述。     

2型糖尿病与恶性肿瘤

2型糖尿病不仅是一个严重的健康问题，还与恶性肿瘤有着密切的联系。近年来流行病学研究证实2型糖尿病与一些常见恶性肿瘤如结、直肠癌、肝癌、胰腺癌、乳腺癌以及子宫内膜癌的发病有关，但其关联的确切机理仍无定论，可能与高血糖、胰岛素及胰岛素样生长因子、内皮素、脂联素、微量元素、激素和药物等诸多因素有关。     

糖尿病与消化系肿瘤关系的研究进展

近年来,随着对消化系肿瘤研究的不断深入,糖尿病与消化系肿瘤的关系越来越受到学者们的关注。目前国外大量流行病学调查研究表明:糖尿病患者消化系肿瘤(包括结直肠癌、胰腺癌、原发性肝癌等)的发病率明显增加。2型糖尿病诱发消化系统肿瘤的可能机制包括:(1)胰岛素样生长因子1的作用;(2)高胰岛素血症和胰岛素抵抗的作用;(3)宿主免疫功能紊乱;(4)长期高血糖的作用;(5)遗传因素和致癌因素长期作用及微量元素失衡等多方面因素协同作用。     

OLETF大鼠肝脏、肌肉、脂肪组织中胰岛素受体底物的蛋白表达

各种靶组织的胰岛素抵抗和胰腺β细胞分泌功能受损是导致2型糖尿病的主要原因[1],但机制不明;为探讨2型糖尿病胰岛素抵抗的分子机制,以一种自发发病的2型糖尿病模型-OLETF大鼠为对象,研究其肝脏、骨胳肌、脂肪组织内胰岛素信号传导分子胰岛素受体底物1(IRS-1)蛋白表达水平.     

IGF-1、IGF-BP-1、IGF-BP-3与糖尿病及糖尿病微血管并发症

糖尿病影响循环中胰岛素样生长因子的水平和活性,不同类型的糖尿病对胰岛素样生长因子活性的影响是不同的.糖尿病患者体内胰岛素样生长因子的紊乱,可能参与糖尿病肾病、糖尿病视网膜病变的发生、发展.胰岛素样生长因子结合球蛋白-1可能对微血管病变起保护作用,胰岛素样生长因子结合球蛋白-3参与微血管病变的发病机制不明.     

2型糖尿病和动脉粥样硬化性心血管病的关系

动脉粥样硬化性心血管病是2型糖尿病患者死亡和残疾的主要原因,2型糖尿病患者发生动脉粥样硬化病变的风险显著高于非糖尿病患者。虽然目前关于2型糖尿病与动脉粥样硬化发生和发展之间的关系尚未完全阐明,但大量基础与临床研究已证实二者之间存在密切的内在联系。现有研究提示,2型糖尿病患者发生动脉粥样硬化病变的机制可能涉及高血糖、胰岛素抵抗、血管钙化、氧化应激、内皮功能障碍和炎症反应等。结合近年来最新的研究结果,现总结分析2型糖尿病与动脉粥样硬化性心血管病之间的潜在联系与可能机制。     

糖尿病是一种炎症性疾病?

在2型糖尿病的发生发展中，炎症因子可能具有重要作用。炎症因子与脂肪内分泌、氧化应激、免疫系统相互作用引起胰岛素抵抗和β细胞结构与功能的障碍，并导致2型糖尿病。炎症学说的提出为糖尿病的发病机制和开发预防糖尿病新药提供了又一个新的研究方向。．     

胰岛素样生长因子与糖尿病脑病

胰岛素样生长因子是一类结构上与胰岛素部分同源并具有胰岛素样活性的多肽,广泛分布于中枢和外周神经系统,具有神经营养作用。近年来研究发现,胰岛素样生长因子与糖尿病脑病密切相关,胰岛素样生因子水平下降可引起糖尿病脑病患者认知功能受损,补充胰岛素样生长因子可能对糖尿病脑病认知功能的改善有治疗作用。     

肺癌合并2型糖尿病围手术期血糖管理

目的探讨肺癌合并2型糖尿病患者术后不同血糖控制方案的疗效。方法选择61例肺癌合并2型糖尿病的患者,随机分为3组:静脉输注组、胰岛素泵组和甘精胰岛素组。于术后检测3组各项临床指标。结果治疗后甘精胰岛素组在血糖控制时间、治疗后日平均血糖、胰岛素日使用量、低血糖的发生率及血糖波动程度、胰岛素抵抗指数等方面与胰岛素泵组无差异,但均显著低于静脉胰岛素输注组。结论肺癌合并2型糖尿病患者在围术期采用甘精胰岛素和胰岛素泵治疗均可安全有效的控制血糖。     

2型糖尿病与肺癌

2型糖尿病与肺癌均是常见病及多发病,两者之间存在联系,2型糖尿病患者肿瘤的发病率升高,高血糖、胰岛素抵抗、免疫功能破坏、脂肪细胞因子等均与肺癌发病率增高有关。关注两者关系,这将为糖尿病患者肿瘤的预防及控制提供新的方向及途径。本文主要就2型糖尿病与肺癌的关系作一综述。     

酮症倾向糖尿病研究进展

酮症倾向糖尿病是一种异质性综合征,包括1型糖尿病和酮症倾向的2型糖尿病.后者的发病机制可能同糖、脂毒性所导致的严重外周胰岛素抵抗,胰岛β细胞凋亡或功能异常以及某些遗传缺陷有密切的关系.其临床特点是起病急,以酮症为首发症状.1型糖尿病需胰岛素终身治疗,对于酮症倾向的2型糖尿病,其发病机制、分型以及治疗尚无统一的标准.通过对其深入研究,有助于对糖尿病发病机制的认识及治疗方案的制订.     

Vascular, metabolic, and inflammatory abnormalities in normoglycemic offspring of patients with type 2 diabetes mellitus

Endothelial dysfunction, insulin resistance, and elevated levels of circulating proinflammatory markers are among the earliest detectable abnormalities in people at risk for atherosclerosis. Accelerated atherosclerosis is a leading contributor to morbidity and mortality in type 2 diabetes mellitus, a complex genetic disorder. Therefore, we hypothesized that normoglycemic offspring of patients with type 2 diabetes mellitus (NOPD) may have impaired vascular and metabolic function related to an enhanced proinflammatory state. We compared NOPD (n = 51) with matched healthy control subjects without family history of diabetes (n = 35). Flow- and nitroglycerin-mediated brachial artery vasodilation were assessed by ultrasound to evaluate endothelium-dependent and -independent vascular function. Each subject also underwent an oral glucose tolerance test to evaluate metabolic function. Fasting levels of plasma adiponectin and circulating markers of inflammation (high-sensitivity C-reactive protein, CD40 ligand, interleukin 1beta, tumor necrosis factor alpha, vascular cell adhesion molecule 1, and intracellular adhesion molecule) were measured. Both NOPD and the control group had fasting glucose and insulin levels well within the reference range. However, results from oral glucose tolerance test and quantitative insulin sensitivity check index revealed that NOPD were insulin resistant with significantly impaired flow- and nitroglycerin-mediated dilation compared with the control group. Adiponectin levels were lower, whereas many circulating markers of inflammation were higher, in NOPD compared with the control group. Normoglycemic offspring of patients with type 2 diabetes mellitus have impaired vascular and metabolic function accompanied by an enhanced proinflammatory state that may contribute to their increased risk of diabetes and its vascular complications.     

维生素D和糖尿病

维生素D最重要的功能是维持人体钙离子代谢的平衡。随着研究的深入，维生素D在炎性反应、自身免疫性疾病、胰岛素分泌及胰岛素抵抗等方面的作用已经成为研究的热点。维生素D缺乏或不足与糖尿病发病相关。维生素D可通过抑制炎性反应、促进胰岛素释放、减轻胰岛素抵抗等机制参与糖尿病的发病。大量的临床研究发现补充足量的维生素D不仅可以减少1型糖尿病和2型糖尿病的发病，而且还可以改善糖代谢，控制糖尿病相关症状。因此，维生素D可能在预防和控制糖尿病中起重要作用。     

维生素D和糖尿病

维生素D最重要的功能是维持人体钙离子代谢的平衡.随着研究的深入,维生素D在炎性反应、自身免疫性疾病、胰岛素分泌及胰岛素抵抗等方面的作用已经成为研究的热点.维生素D缺乏或不足与糖尿病发病相关.维生素D可通过抑制炎性反应、促进胰岛素释放、减轻胰岛素抵抗等机制参与糖尿病的发病.大量的临床研究发现补充足量的维生素D不仅可以减少...     

Insulin therapy and colorectal cancer risk among type 2 diabetes mellitus patients

BACKGROUND & AIMS: Endogenous hyperinsulinemia in the context of type 2 diabetes mellitus is potentially associated with an increased risk of colorectal cancer. We aimed to determine whether insulin therapy might increase the risk of colorectal cancer among type 2 diabetes mellitus patients. METHODS: We conducted a retrospective cohort study among all patients with a diagnosis of type 2 diabetes mellitus in the General Practice Research Database from the United Kingdom. We excluded patients with <3 years of colorectal cancer-free database follow-up after the diabetes diagnosis as well as those insulin users who developed colorectal cancer after <1 year of insulin therapy. The remaining insulin users and the noninsulin-using type 2 diabetic patients were followed for the occurrence of colorectal cancer. Hazard ratios (HR) were determined in Cox proportional hazard analysis. A nested case-control study was conducted to perform multivariable analysis and to determine a duration-response effect. RESULTS: The incidence of colorectal cancer in insulin users (n = 3160) was 197 per 100,000 person-years, compared with 124 per 100,000 person-years in type 2 diabetes mellitus patients not receiving insulin (n = 21,758). The age- and sex-adjusted HR of colorectal cancer associated with > or =1 year of insulin use was 2.1 (95% CI: 1.2-3.4, P = 0.005). The positive association strengthened after adjusting for potential confounders. The multivariable odds ratio associated with each incremental year of insulin therapy was 1.21 (95% CI: 1.03-1.42, P = 0.02). CONCLUSIONS: Chronic insulin therapy significantly increases the risk of colorectal cancer among type 2 diabetes mellitus patients.     

Pharmacologic therapy for type 2 diabetes mellitus.

Type 2 diabetes mellitus is a chronic metabolic disorder that results from defects in both insulin secretion and insulin action. An elevated rate of basal hepatic glucose production in the presence of hyperinsulinemia is the primary cause of fasting hyperglycemia; after a meal, impaired suppression of hepatic glucose production by insulin and decreased insulin-mediated glucose uptake by muscle contribute almost equally to postprandial hyperglycemia. In the United States, five classes of oral agents, each of which works through a different mechanism of action, are currently available to improve glycemic control in patients with type 2 diabetes. The recently completed United Kingdom Prospective Diabetes Study (UKPDS) has shown that type 2 diabetes mellitus is a progressive disorder that can be treated initially with oral agent monotherapy but will eventually require the addition of other oral agents, and that in many patients, insulin therapy will be needed to achieve targeted glycemic levels. In the UKPDS, improved glycemic control, irrespective of the agent used (sulfonylureas, metformin, or insulin), decreased the incidence of microvascular complications (retinopathy, neuropathy, and nephropathy). This review examines the goals of antihyperglycemic therapy and reviews the mechanism of action, efficacy, nonglycemic benefits, cost, and safety profile of each of the five approved classes of oral agents. A rationale for the use of these oral agents as monotherapy, in combination with each other, and in combination with insulin is provided.